Am. J. Respir. Cell Mol. Biol., Volume 23, Number 2, August, 2000 188-193

A Novel Nonclassic 2-Microglobulin-Restricted Mechanism Influencing Early Lymphocyte Accumulation and Subsequent Resistance to Tuberculosis in the Lung

Celine D. D'Souza, Andrea M. Cooper, Anthony A. Frank, Stefan Ehlers, Joanne Turner, Albert Bendelac, and Ian M. Orme

Mycobacterial Research Laboratories, Departments of Microbiology and Pathology, Colorado State University, Fort Collins, Colorado; Division of Molecular Infection Biology, Research Center Borstel, Center for Medicine and Biosciences, Borstel, Germany; and Department of Molecular Biology, Princeton University, Princeton, New Jersey

In this study, we compared the course of a low-dose aerosol Mycobacterium tuberculosis infection in mice bearing gene disruptions for the 2-microglobulin molecule, the CD8 molecule, and the CD1 molecule. Over the first 50 d of infection, the CD8- and CD1-disrupted mice were no more susceptible to infection than were the control mice. In contrast, the bacterial load in 2-microglobulin gene-disrupted mice increased rapidly and attained much higher levels than that observed in the other gene-disrupted mice and in control mice. A second major difference between the 2-microglobulin gene-disrupted mice and the other animals was the development of lung granulomas; both the CD8- and CD1-disrupted mice developed essentially normal granulomas except for an apparent increased lymphocyte influx in the CD8-disrupted mice. The 2-microglobulin gene-disrupted mice, on the other hand, developed granulomas virtually devoid of lymphocytes, with these cells instead localized within prominent perivascular cuffing adjacent to the lesions. These data support the hypothesis that a 2-microglobulin-dependent, non-CD8- and non-CD1-dependent mechanism controls the early and efficient influx of protective lymphocytes into infected lesions, and that the absence of this mechanism decreases the capacity of the animal to initially deal with pulmonary tuberculosis.

This article has been cited by other articles:

				A. L. Cogen and T. A. Moore {beta}2-Microglobulin-Dependent Bacterial Clearance and Survival during Murine Klebsiella pneumoniae Bacteremia Infect. Immun., January 1, 2009; 77(1): 360 - 366. [Abstract] [Full Text] [PDF]

				B. Sherry, W. W. Dai, M. L. Lesser, and H. Trachtman Dysregulated Chemokine Receptor Expression and Chemokine-Mediated Cell Trafficking in Pediatric Patients with ESRD Clin. J. Am. Soc. Nephrol., March 1, 2008; 3(2): 397 - 406. [Abstract] [Full Text] [PDF]

				A. Bafica, C. A. Scanga, C. G. Feng, C. Leifer, A. Cheever, and A. Sher TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis J. Exp. Med., December 19, 2005; 202(12): 1715 - 1724. [Abstract] [Full Text] [PDF]

				M. Gonzalez-Juarrero, J. M. Hattle, A. Izzo, A. P. Junqueira-Kipnis, T. S. Shim, B. C. Trapnell, A. M. Cooper, and I. M. Orme Disruption of granulocyte macrophage-colony stimulating factor production in the lungs severely affects the ability of mice to control Mycobacterium tuberculosis infection J. Leukoc. Biol., June 1, 2005; 77(6): 914 - 922. [Abstract] [Full Text] [PDF]

				A. P. Junqueira-Kipnis, A. Kipnis, A. Jamieson, M. G. Juarrero, A. Diefenbach, D. H. Raulet, J. Turner, and I. M. Orme NK Cells Respond to Pulmonary Infection with Mycobacterium tuberculosis, but Play a Minimal Role in Protection J. Immunol., December 1, 2003; 171(11): 6039 - 6045. [Abstract] [Full Text] [PDF]

				M. Skold and S. M. Behar Role of CD1d-Restricted NKT Cells in Microbial Immunity Infect. Immun., October 1, 2003; 71(10): 5447 - 5455. [Full Text] [PDF]

				O. C. Turner, R. G. Keefe, I. Sugawara, H. Yamada, and I. M. Orme SWR Mice Are Highly Susceptible to Pulmonary Infection with Mycobacterium tuberculosis Infect. Immun., September 1, 2003; 71(9): 5266 - 5272. [Abstract] [Full Text] [PDF]

				F. Dieli, M. Taniguchi, M. Kronenberg, S. Sidobre, J. Ivanyi, L. Fattorini, E. Iona, G. Orefici, G. De Leo, D. Russo, et al. An Anti-Inflammatory Role for V{alpha}14 NK T cells in Mycobacterium bovis Bacillus Calmette-Guerin-Infected Mice J. Immunol., August 15, 2003; 171(4): 1961 - 1968. [Abstract] [Full Text] [PDF]

				K. B. Urdahl, D. Liggitt, and M. J. Bevan CD8+ T Cells Accumulate in the Lungs of Mycobacterium tuberculosis-Infected Kb-/-Db-/- Mice, But Provide Minimal Protection J. Immunol., February 15, 2003; 170(4): 1987 - 1994. [Abstract] [Full Text] [PDF]

				U. E. Schaible, H. L. Collins, F. Priem, and S. H.E. Kaufmann Correction of the Iron Overload Defect in {beta}-2-Microglobulin Knockout Mice by Lactoferrin Abolishes Their Increased Susceptibility to Tuberculosis J. Exp. Med., December 2, 2002; 196(11): 1507 - 1513. [Abstract] [Full Text] [PDF]

				A. Chackerian, J. Alt, V. Perera, and S. M. Behar Activation of NKT Cells Protects Mice from Tuberculosis Infect. Immun., November 1, 2002; 70(11): 6302 - 6309. [Abstract] [Full Text] [PDF]

				V. Lazarevic and J. Flynn CD8+ T Cells in Tuberculosis Am. J. Respir. Crit. Care Med., October 15, 2002; 166(8): 1116 - 1121. [Full Text] [PDF]

				V. Gruppo, O. C. Turner, I. M. Orme, and J. Turner Reduced up-regulation of memory and adhesion/integrin molecules in susceptible mice and poor expression of immunity to pulmonary tuberculosis Microbiology, October 1, 2002; 148(10): 2959 - 2966. [Abstract] [Full Text] [PDF]

				J. Turner, A. A. Frank, and I. M. Orme Old Mice Express a Transient Early Resistance to Pulmonary Tuberculosis That Is Mediated by CD8 T Cells Infect. Immun., August 1, 2002; 70(8): 4628 - 4637. [Abstract] [Full Text] [PDF]

				I. M. Orme The search for new vaccines against tuberculosis J. Leukoc. Biol., July 1, 2001; 70(1): 1 - 10. [Abstract] [Full Text] [PDF]

				S.-H. Park, A. Weiss, K. Benlagha, T. Kyin, L. Teyton, and A. Bendelac The Mouse Cd1d-Restricted Repertoire Is Dominated by a Few Autoreactive T Cell Receptor Families J. Exp. Med., April 16, 2001; 193(8): 893 - 904. [Abstract] [Full Text] [PDF]

				J. Turner, C. D. D'Souza, J. E. Pearl, P. Marietta, M. Noel, A. A. Frank, R. Appelberg, I. M. Orme, and A. M. Cooper CD8- and CD95/95L-Dependent Mechanisms of Resistance in Mice with Chronic Pulmonary Tuberculosis Am. J. Respir. Cell Mol. Biol., February 1, 2001; 24(2): 203 - 209. [Abstract] [Full Text]

				A. M. Cooper, J. E. Pearl, J. V. Brooks, S. Ehlers, and I. M. Orme Expression of the Nitric Oxide Synthase 2 Gene Is Not Essential for Early Control of Mycobacterium tuberculosis in the Murine Lung Infect. Immun., December 1, 2000; 68(12): 6879 - 6882. [Abstract] [Full Text] [PDF]